The wide-scale use of nuclear technology in power production and in nuclear weapons manufacturing has necessitated the periodic monitoring of biological and environmental samples for the presence of selected elements such as strontium (Sr), cerium (Ce), europium (Eu), actinium (Ac), thorium (Th), uranium (U,) neptunium (Np), plutonium (Pu), americium (Am), and curium (Cm), and for monitoring particular nuclides such as 90Sr, 144Ce, and 152, 154Eu. There is, therefore, a clear need for an analytical procedure and methodology suitable for use in the routine monitoring of persons whose activities expose them to the risk of internal contamination from these elements and for the determination of the levels of radionuclides in various environmental samples (e.g., soils, plants, natural waters, and waste streams). A number of procedures for the selective recovery of the above elements have been disclosed.
U.S. Pat. No. 4,548,790 dated Oct. 22, 1985 describes a group of neutral bifunctional organophosphorus compounds broadly described as alkyl (phenyl)-N,N-dialkylcarbamoylmethylphosphine oxides (hereinafter referred to as CMPO) that are useful for the recovery of actinide and lanthanide cations from acidic solutions. The combination of the CMPO with a phase modifier such as tri-n-butyl phosphate (hereinafter referred to as TBP) in a normal paraffin hydrocarbon diluent is described in U.S. Pat. No. 4,574,072 dated Mar. 4, 1986.
U.S. Pat. No. 4,835,107 dated Oct. 21, 1986 describes a method for the concentration and separation of actinide cations from biological and environmental samples using CMPO and TBP in a chromatographic mode. The CMPO/TBP chromatographic system was applied in the recovery and purification of yttrium-90 for medical applications described in U.S. Pat. No. 5,368,736 dated Nov. 29, 1994. Other systems utilizing monofunctional, as well as bifunctional, organophosphorus extractants in the recovery of lanthanide and actinide cations from acidic media in both the liquid-liquid extraction mode and in the extraction chromatographic mode are described in Kimura (1990) J. Radioanal. Nucl. Chem., 141, 295 and Ramanujam et al. (1995) Solvent Extr. Ion Exch., 13(2), 301-312 U.S. Pat. Nos. 5,100,585, 5,110,474 and 5,346,618 by some of the present inventors teach the manufacture and use of a chromatographic medium for selectively separating strontium or technetium cations from acidic compositions from various sources. The solid phase chromatographic medium made and used in those patents comprised a solution of a Crown ether dissolved in a diluent that was slightly soluble or insoluble in water, but capable of dissolving a substantial quantity of water, such as octanol, which solution was itself dispersed onto a solid inert resin substrate material.
A few years after the filing of the applications that became the above U.S. patents, Benzi et al. (1992) J. Radioanal. Nucl. Chem., Letters, 164(4):211-220 reported on the use of 18-Crown-6 (18C6), dibenzo-18-Crown-6 (DB18C6) and 24-Crown-8 (24C8) as well as open chain ligands (podands) adsorbed on Amberlite® XAD-4 and XAD-7 resins or Kieselgel as supports for removal of radium cations from aqueous solutions. Those authors reported the supported crown ethers to be inefficient for that extraction, whereas the supported open chain ligands were said to provide satisfactory distribution coefficients for the removal of radium.
The above-noted patents of some of the present inventors provided a large technological advance over the liquid-liquid separation techniques that preceded them, and from which their technical advance grew. However, the separation medium of those patents exhibited changes upon elution of the captured strontium cations that minimized their usefulness for a subsequent separation, including loss of diluent to the effluent medium. Still further, the amount of strontium cation-extracting Crown ether present on any given support was limited because of the presence of the diluent.
All of the prior methods suffer from one or more major disadvantages. Foremost among these is that the retention of the trivalent lanthanides and actinides in acidic aqueous nitric and hydrochloric acid is limiting and the subsequent recovery in dilute acid is difficult, especially in the case of tetra- and hexavalent actinides. In the chromatographic mode, low retention of the analyte in the column loading step results in its early breakthrough in the column effluent. Early breakthrough frequently results in losses of analyte and insufficient purification because of limited column rinsing capabilities.
In recent years, the wide-scale use of nuclear technology has also expanded greatly in the field of medicine. The use of radioactive materials in diagnostic medicine is now readily accepted because these procedures are safe, minimally invasive, cost-effective, and they provide unique information that is otherwise unavailable to the clinician. More recently, radioactive isotopes are being used to treat disease as opposed to diagnosing disease. This technique is referred to as radioimmunotherapy (RIT). The U.S. Food and Drug Administration (FDA) has approved the use of the first RIT drug that relies on radioactive decay to impart the cytotoxic effect to the disease site.
The FDA has mandated rigorous purity requirements for radionuclides used for therapeutic applications. Foremost among these requirements is high radionuclidic purity, which stems directly from the hazards associated with the introduction of long-lived or high-energy radioactive impurities into a patient. Chemical purity is also vital to a safe and efficient medical procedure because the radionuclide must generally be bonded to a biolocalizing agent prior to use. Biolocalizing agents have extremely low capacities for metal ions and, therefore, the presence of ionic interferents can inhibit the uptake of the medically useful radionuclide. Another critical factor in bonding the radionuclide to the biolocalizing agent is obtaining the desired purified radionuclide in a dilute ≦0.1 M acidic (usually HCl) aqueous solution. A number of pseudo-lanthanide, prelanthanide, lanthanide, preactinide and actinide nuclides are candidates for use in radioimmunotherapy; for example, 47Sc, 90Y, 149Pm, 153Sm, 153Gd, 166Ho, 177Lu, 225Ac, and 255Fm.
In related studies, Sasaki et al. [Sasaki et al. (2001) Solvent Extr. Ion Exch., 19(1):91-103; and Sasaki et al. (2002) Solvent Extr. Ion Exch., 20(1):21-34. See also the web site of the Japanese Atomic Energy Research Institute (JAERI) and Japanese Kokai No. 2002-1007 and No. 2002-243890.] have published results on the liquid-liquid extraction of trivalent lanthanides and tri-, tetra-, and hexavalent actinides with structurally tailored diamides including selected diglycolamides. However, these studies were carried out using very dilute solutions of the extractants in nitrobenzene, chloroform, toluene, hexane, or n-dodecane. The aqueous phase was primarily nitric acid or 0.1 M sodium perchlorate and, in the case of trivalent lanthanides and actinides, never exceeded 1 M in concentration. Extrapolation of these data to a useful extraction chromatographic system that can achieve the objectives cited herein cannot be done.
It has been demonstrated in related studies by Cortina et al. (1994) Solvent Extr. Ion Exch., 12(2):371-391, that quantitative predictions of metal ion uptake from liquid-liquid extraction data cannot be extended to extraction chromatographic systems. These studies have shown that the selectivity order for the extraction of Cu and Cd (Cu greater than Cd) by bis-2-ethylhexyl phosphoric acid (HDEHP) is reversed for the solid supported reagent. Studies by Miralles et al. (1992) Solvent Extr. Ion Exch. 10(1):51-68 and Casas et al. (1989) Polyhedron 8:2535 have shown that the nature of the metal species extracted by HDEHP in toluene or paraffinic hydrocarbons is somewhat different from the same extractant sorbed on Amberlite® XAD-2. The extracted species is typically less solvated in the extraction chromatographic system than in the liquid-liquid extraction system. None of the above observations are surprising because the film thickness of an extractant sorbed on a porous solid support having a surface area of 400 to 500 m2/g, for example Amberchrom® CG-71, and containing 40 weight percent of an extractant with a density of 0.95 g/mL is only about 1 to 2×10−3μm. It is not, therefore, unexpected that the physical and chemical properties of the extractant and the concomitant extraction behavior in extraction chromatographic resins are different than in a liquid-liquid extractant system.
It would therefore be beneficial to provide a method, separation medium and apparatus for separating multivalent cations from acidic aqueous samples such as biological, commercial waste and environmental samples that do not exhibit the negative attributes of the prior technologies. The method, separation medium and apparatus of the present invention that are described hereinafter can overcome those negative attributes, while maintaining the previously achieved advances.